The proposal requests support to purchase a Matrix Assisted Laser Desorption Ionization-Time of Flight-Mass Spectrometer (MALDI-TOF MS) for use at Children's Hospital Oakland Research Institute (CHORI) to facilitate an array of projects involving single nucleotide polymorphism (SNP) and proteome analysis. We emphasize the appropriateness of the MALDI-TOF MS approach compared to other technologies, the value of this addition to enhancing our research efforts, and the timeliness in the adoption of this technology to the proposed research applications. MALDI-TOF MS offers an efficient means of identifying SNPs, the most common type of DNA sequence variations in human populations, using high throughput multiplex technology populations. Multiplex analysis, allows simultaneous genotyping of a single sample at multi loci, and requires a system that is easily adaptable to the changing needs of research. Although alternative approaches to multiplex SNP-based genotyping exist, most of these are considerably more time consuming and less flexible. Use the multiplex SNP analysis technique afforded by MALDI-TOF MS, large panels of samples can be typed efficiently, accurately, specifically, and reliably. Acquisition of this instrument will benefit a consortium of users at CHORI who are engaged in a search for genes that modulate disease susceptibility and severity and sensitivity to environmental toxins. Among the diseases under study are sickle cell anemia, thalassemia, nutritional deficiencies, tuberculosis, diabetes, asthma, birth defects, sexually transmitted disease, and trachoma. In a broader context access to MALDI-TOF MS at CHORI will facilitate the application of knowledge regarding the role of genetic variations in human health. Proteomics, the large scale analysis of proteins, complements genomics by focusing on the gene products responsible for mediating cellular function. Proteomics focuses on several aspects of protein analysis: the identification of proteins and their post-translational modifications, the "differential display" utilized in comparing protein expression in health and disease states, and the studies of protein-protein interactions required to elucidate structure and function. MALDI-TOF MS is a well- established and robust which fulfills all of the proteomic functions described above. The availability of a MALDI-TOF MS instrument with the capabilities to perform these tasks, as well as quantitative analysis using isotope coded affinity tags (ICAT), will greatly enhance our ability to simultaneously characterize multiple proteins potentially involved mitochondrial function and other physiological states involved in health and disease.